title: SLC45A2 mutation frequency in Oculocutaneous Albinism Italian patients doesn't differ from other European studies.
abstract: BACKGROUND
  Oculocutaneous Albinism (OCA) is a heterogeneous group of inherited diseases involving hair, skin and eyes. To date, six forms are recognized on the effects of different melanogenesis genes. OCA4 is caused by mutations in SLC45A2 showing a heterogeneous phenotype ranging from white hair, blue irides and nystagmus to brown/black hair, brown irides and no nystagmus. The high clinic variety often leads to misdiagnosis. Our aim is to contribute to OCA4 diagnosis defining SLC45A2 genetic variants in Italian patients with OCA without any TYR, OCA2 and TYRP1 gene defects.
  
  
  METHODS
  After the clinical diagnosis of OCA, all patients received genetic counseling and genetic test. Automatic sequencing of TYR, OCA2, and TYRP1 genes was performed on DNA of 117 albino patients. Multiplex Ligation-dependent Probe Amplification (MLPA) was carried out on TYR and OCA2 genes to increase the mutation rate. SLC45A2 gene sequencing was then executed in the patients with a single mutation in one of the TYR, OCA2, TYRP1 genes and in the patients, which resulted negative at the screening of these genes.
  
  
  RESULTS
  SLC45A2 gene analysis was performed in 41 patients and gene alterations were found in 5 patients. Four previously reported SLC45A2 mutations were found: p.G100S, p.W202C, p.A511E and c.986delC, and three novel variants were identified: p.M265L, p.H94D, and c.1156+1G>A. All the alterations have been detected in the group of patients without mutations in the other OCA genes.
  
  
  CONCLUSIONS
  Three new variants were identified in OCA4 gene; the analysis allowed the classification of a patient previously misdiagnosed as OA1 because of skin and hair pigmentation presence. The molecular defects in SLC45A2 gene represent the 3.4% in this cohort of Italian patients, similar to other Caucasian populations; our data differ from those previously published by an Italian researcher group, obtained on a smaller cohort of patients.
authors.affiliation: Medical Genetics Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mauri
authors.forename: Luca
authors.initials: L
authors.lastname: Barone
authors.forename: Muna
authors.initials: M
authors.lastname: Al Oum
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Longo
authors.forename: Elena
authors.initials: E
authors.lastname: Piozzi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Manfredini
authors.forename: Franco
authors.initials: F
authors.lastname: Stanzial
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedicenti
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Patrosso
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human
keywords: Albinism; C10orf11; DCT; DNA complementary to RNA; HDD; HVD; Human Diversity Database; Human Variation Database; Novel variants; OA1; OCA; OCA2; OCA4; OCT; SLC24A5; SLC45A2; TYR; TYRP1; cDNA; chromosome 10 open reading frame 11 [Homo sapiens (human)]; dopachrome tautomerase [Homo sapiens (human)]; ocular albinism type 1; oculocutaneous albinism; oculocutaneous albinism II [Homo sapiens (human)]; optical coherence tomography; solute carrier family 24 (sodium/potassium/calcium exchanger), member 5 [Homo sapiens (human)]; solute carrier family 45, member 2 [Homo sapiens (human)] coding for MATP (membrane-associated transporter protein); tyrosinase [Homo sapiens (human)]; tyrosinase-related protein 1 [Homo sapiens (human)]; wild type; wt